Evolution of HCV associated porphyria cutanea tarda after HCV sustained virologic response by direct acting antivirals.

OBJECTIVES: Porphyria cutanea tarda (PCT) is common and usually associated with HCV chronic infection and HFE polymorphisms. Since DAA IFN-free regimens availability, SVR for HCV is nearly a constant and we wonder whether HCV SVR determine PCT evolution. METHODS: Retrospective observational study including patients with HCV associated PCT from the Gastroenterology and Infectious Diseases Departments at our Hospital, treated with DAA (Apr/2015-Apr/2017). Clinical variables of PCT were collected at PCT diagnosis, after PCT treatment, before DAA use and after SVR achievement. UROD activity and C282Y/H63D polymorphisms were registered. SPSS 22.0. RESULTS: 13 HCV-PCT patients included: median age 52.5 years; 4 females; 8 HCV/HIV co-infected (all on undetectable viral load). Classical PCT factors: 12 smoked, 9 alcohol abuse, 6 former IDU. 10 type I PCT and 1 type II PCT. HFE polymorphism: 2 cases with C282Y/H63D; H63D polymorphism in 8. PCT manifestations resolved with PCT treatment in 4 patients, almost completely in 7 patients, 1 patient referred stabilization and one worsened. After DAA treatment all the residual lesions resolved, what always led to specific treatment interruption. CONCLUSIONS: Our series of cases of HCV-associated PCT shows that SVR after DAA treatment leads to PCT resolution. Porphyrin levels are not needed after ending PCT specific treatment interruption when there are no residual skin lesions in HCV-associated PCT.

Functional analysis of new variants at the low-density lipoprotein receptor associated with familial hypercholesterolemia.

Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, and PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study, we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO-ldlA7 cells. The LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684 G>T;694 G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as "uncertain significant variants", and therefore, carry out cascade family screening.

[Stimulation of the centromedian nucleus in refractory epilepsy associated to ring chromosome 20]. / Estimulacion del nucleo centromediano en la epilepsia farmacorresistente asociada al cromosoma 20 en anillo.

INTRODUCTION: Ring chromosome 20 syndrome is a rare genetic disorder, with a late diagnosis. CASE REPORT: A 43-year-old woman who had had refractory epilepsy since the age of six years, for which she was treated with deep brain stimulation of the centromedian nucleus, and also a ring chromosome 20. CONCLUSIONS: From the findings of the study it can be concluded that deep brain stimulation of the centromedian nucleus is ineffective in patients with ring chromosome, but note must be taken of the importance of genetic characterisation for the management of refractory epilepsy.

TITLE: Estimulacion del nucleo centromediano en la epilepsia farmacorresistente asociada al cromosoma 20 en anillo.Introduccion. El sindrome del cromosoma 20 en anillo es una alteracion genetica infrecuente, con un diagnostico tardio. Caso clinico. Mujer de 43 años con epilepsia farmacorresistente desde los 6 años, tratada mediante estimulacion cerebral profunda del nucleo centromediano y con un cromosoma 20 en anillo. Conclusiones. Del estudio se extrae la conclusion de la inefectividad de la estimulacion cerebral profunda del nucleo centromediano en pacientes con cromosoma en anillo, pero se apunta la importancia de la caracterizacion genetica para el manejo de la epilepsia farmacorresistente.

[Accidental finding of a cri du chat syndrome in an adult patient by means of array-CGH]. / Hallazgo inesperado de sindrome cri du chat en una paciente adulta mediante array-CGH.

INTRODUCTION: The cri du chat syndrome (CDCS) come from a partial or total deletion of the short arm of chromosome 5, being one of the most common deletion syndromes in human beings. The great majority of patients are diagnosed between the first month and first year of life, but herein we report a finding of a CDCS in a woman with a suspect of spinocerebellar ataxia, and a family medical record of ataxia and bipolar disorder. We pay special attention to the clinical features as well as the diagnostics tests, used to identify the CDCS. CASE REPORT: We report a case of a 46 years-old woman showing a borderline intelligence and bilateral cataract surgery at the age of 43. Beginning of symptoms in childhood included hypoacusia, ataxia, dysarthria, dysphagia, depression, cognitive impairment and bipolar disorder. Physical examination showed microcephaly, micrognathia, talipes equinovarus and ataxia. Karyotype and array-CGH were carried out on peripheral blood. The patient showed a rearrangement involving chromosomes 5 and 15, as well as an inversion of chromosome 9: 45,XX,inv9(p11q13);t(5,15)(p15.33;q11.2). Array comparative genomic hybridization was performed showing a 2.91 Mb deletion at 5p15.33, genomic formula arr 5p15.33 (151537-3057771)x1. The deletion involved 20 genes, including TERT gene. CONCLUSIONS: The multiple gene deletions confirmed the CDCS diagnosis, being responsible for the patient phenotype. It has been showed up the importance of using the correct diagnosis techniques (array-CGH, peripheral blood karyotype) as well as their appropriate choice.

TITLE: Hallazgo inesperado de sindrome cri du chat en una paciente adulta mediante array-CGH.Introduccion. El sindrome cri du chat (SCDC) tiene su origen en una delecion parcial o total del brazo corto del cromosoma 5, y es uno de los sindromes de delecion cromosomica mas frecuentes en humanos. La mayoria de los pacientes se diagnostica entre el primer mes y el primer año de vida, si bien aqui se describe el hallazgo de un SCDC en una mujer con sospecha de ataxia espinocerebelar y antecedentes familiares de trastorno bipolar y ataxia, con especial atencion a las caracteristicas clinicas y las tecnicas diagnosticas que permitieron su identificacion. Caso clinico. Mujer de 46 años que presentaba una inteligencia limite, intervenida a los 43 años de faquectomia bilateral. El inicio de la sintomatologia fue durante la infancia, e incluia hipoacusia, ataxia, disartria, disfagia, depresion, deterioro cognitivo y trastorno bipolar. La exploracion fisica revelo microcefalia, micrognatia, pies equinos y ataxia. Se realizo cariotipo y array-CGH en sangre periferica. La paciente presentaba una traslocacion que involucraba los cromosomas 5 y 15, y una inversion del cromosoma 9: 45,XX,inv9(p11q13);t(5,15)(p15.33;q11.2). El array-CGH mostro una delecion de 2,91 Mb en 5p15.33, formula genomica arr 5p15.33 (151537-3057771)x1, que involucraba 20 genes, incluyendo el gen TERT. Conclusiones. La delecion de multiples genes confirmo el diagnostico de SCDC y es la responsable del fenotipo de la paciente. Se pone de manifiesto la importancia de utilizar tecnicas adecuadas de diagnostico (array-CGH, cariotipo en sangre periferica) y la correcta eleccion de estas.

[Electroclinical characteristics of a patient with ring chromosome 20 syndrome]. / Características electroclínicas de un paciente con síndrome del cromosoma 20 en anillo.

INTRODUCTION: The ring chromosome 20 syndrome (r20) is a rare genetic disorder with a late diagnosis. CASE REPORT: A 17 year old boy with drug-resistant epilepsy of 14 years of evolution, which has moderate mental retardation, behavioral alterations and seizures consisting of complex non-convulsive status and generalized seizures during wakefulness, along with more subtle epileptic manifestations during sleep. Karyotype in peripheral blood showed the existence of a ring chromosome 20, whose breakpoints were p13q13.3, presenting a mosaicism 46,XY[23]/46,XY,r(20)(p13q13.3)[25]. CONCLUSIONS: The epileptic r20 syndrome seems to have a characteristic electroclinical phenotype and, although not pathognomonic, should be sufficient for all patients who meet a karyotype in peripheral blood, thus avoiding multiple trials with unnecessary drugs and exhaustive studies. In this sense, the study of sleep EEG may be helpful.

TITLE: Caracteristicas electroclinicas de un paciente con sindrome del cromosoma 20 en anillo.Introduccion. El sindrome del cromosoma 20 en anillo (r20) es una alteracion genetica infrecuente, con un diagnostico tardio. Caso clinico. Varon de 17 años con epilepsia farmacorresistente de 14 años de evolucion, que presentaba retraso mental moderado, alteraciones conductuales y crisis epilepticas consistentes en estados complejos no convulsivos y crisis generalizadas durante la vigilia, junto con manifestaciones epilepticas mas sutiles durante el sueño. El estudio del cariotipo en sangre periferica mostro la existencia de un cromosoma 20 en anillo, cuyos puntos de corte parecen ser p13q13.3, y presento un mosaicismo 46,XY[23]/46,XY,r(20)(p13q13.3)[25]. Conclusiones. El sindrome epileptico r20 parece tener un fenotipo electroclinico caracteristico y, aunque no es patognomonico, deberia ser suficiente para realizar en todos los pacientes que lo cumplan un cariotipo en sangre periferica, que evite asi los multiples ensayos con farmacos y estudios exhaustivos innecesarios. En ese sentido, el estudio electroencefalografico de sueño puede resultar de gran ayuda.

[Significance of complex analysis of electrical activity in temporal lobe epilepsy: foramen ovale electrodes records]. / Análisis complejo de la actividad eléctrica en la epilepsia del lóbulo temporal: registros con electrodos de foramen oval.

INTRODUCTION: Temporal lobe epilepsy (TLE) is commonly associated with the process of synchronisation during the interictal stage, which show up as 'spikes' on neurophysiological recordings, and also with hypersynchronic activity during clinical seizures. Nevertheless, desynchronisation also seems to play an important role in the epileptogenic process, favouring the onset of seizures. AIMS: The aim of this work is to show how the latest complex network analysis techniques applied to the recordings from the foramen ovale electrodes provide valuable new information about the dynamics of mesial activity in TLE. The study also seeks to show that desynchronisation of the mesial activity plays an important role in TLE. PATIENTS AND METHODS: A cluster technique was used to analyse the recordings of six patients with TLE during the interictal stage and two seizures during the ictal period. RESULTS. Electrical activity on the ipsilateral side behaves in a less synchronic manner than that of the contralateral side. There is clearly a greater tendency in the mesial zone of the epileptic side to arrange itself in isolated groups of synchronic activity than on the contralateral side, which is organised in large groups of synchronised activity. CONCLUSIONS: Analysis of the neurophysiological recordings, especially from the foramen ovale electrodes, by cluster and network analysis provides novel information that is not accessible by classical spike analysis. The greater degree of desynchronisation on the ipsilateral side would favour the appearance and origin of the seizures on that side.

[Family history of epilepsy resistant to treatment]. / Antecedentes familiares en epilepsias refractarias al tratamiento.

INTRODUCTION: Family aggregation can help determine the risk of epilepsy among relatives. Our aims are to describe the prevalence of family precedents of epilepsy among the diagnosed patients' relatives of the first and second degree, and to look for an association with diverse clinical variables. PATIENTS AND METHODS: Market descriptive prospective study in a transverse cohort of a Spanish population. The study included 71 patients who, besides fulfilling the clinical diagnostic criteria, had a video-electroencephalogram compatible with epilepsy and drug resistance. The following variables were gathered: the first or second degree of family history, the location (temporal lateral, temporal mesial, parietal, frontal) of the epileptic abnormality, age at diagnosis, and type of epilepsy. The frequency and percentage were calculated of every variable. The probability of recurrence in a relative of the first or second degree was calculated by means of the relative risk (RR). RESULTS: On the whole, the gender distribution was 34 (47.9%) males and 37 (52.1%) females, with ages of 28.3 ± 10.3 years and 34.3 ± 10.2 years, respectively. The prevalence of family aggregation of epilepsy was 28 (34.9%). Family aggregation was more probable among males (RR = 2.5), when the diagnosis of epilepsy was realized between 13 and 18 years old (RR = 1.7), or when the epileptogenic area is located in the temporal mesial zone (RR = 1.9). CONCLUSIONS: Our study supports the existence of increased risk of epilepsy among relatives of drug-resistant epileptic patients.

[Differential contribution of preoperatory studies to diagnosis in temporal lobe epilepsy surgery]. / Contribución diferencial de los estudios preoperatorios al diagnostico en la cirugia de la epilepsia temporal.

INTRODUCTION: It is necessary to know the degree of concordance of preoperative studies in temporal lobe epilepsy (TLE). AIM. To analyze the relative importance of different preoperative tests (vEEG, EEG, SPECT and MRI), the degree of agreement between them, and to develop a Bayesian probability model for diagnosis. PATIENTS AND METHODS: We analyzed 73 patients operated by TLE, with a minimum postoperative follow-up of two years. To analyze the localization capability of different test, we used only patients with an Engel's grade I outcome during all the follow-up time (n = 60). RESULTS: Engel's grades percentages at 2 years were 87.7/8.2/3.0/0.0 (I/II/III/IV, respectively). The preoperative correlation was < 50% for three tests and 33% for the four. MRI studies were found normal in 33.3% of cases. According to the localization index, the arrange was vEEG > RM > SPECT > EEG. The conditional probability of correct localization for a test was vEEG (0.950) > EEG (0.719) > SPECT (0.717) > RM (0.683). Concordance for more than two tests, was = 0.587 (vEEG + MRI). The probability of obtaining a priori correct localization was vEEG (0.983) > RM (0.414) > EEG (0.285) > SPECT (0.209). The Bayesian model is highly reliable. CONCLUSIONS: Probably it is not always possible to obtain a high degree of agreement among preoperative test, despite this, it is possible to obtain a good functional result. The most effective test is the vEEG.